Article

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

Upadacitinib in the management of Crohn's disease and novel data challenging standard clinical practice are some of the inflammatory bowel disease (IBD) highlights from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School, Boston, Massachusetts.

Dr Feuerstein begins by discussing two studies of upadacitinib induction and maintenance in Crohn's disease. Both studies showed that the drug achieved higher fistula closure and remission rates than did placebo, regardless of prior biologic therapy exposure.

The third study chosen by Dr Feuerstein asks whether early resection of ileocecal Crohn's disease might achieve better outcomes than would standard anti–tumor necrosis factor therapy. The study results suggested that early resection could postpone the need for medication for longer than previously thought.

More potentially practice-changing data comes from the SuPREMe-CD study, which showed that using Kono-S anastomosis reduced endoscopic recurrence of Crohn's disease compared with traditional side-to-side anastomosis.

Dr Feuerstein next discusses an analysis of the SAPPHIRE Registry, which found that IBD treatments were not linked to cancer risk. In closing, he reports on a study that showed longer withdrawal time during colonoscopy, meaning longer time spent examining the colon, is associated with improved detection of polypoid dysplasia.

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships.

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Upadacitinib in the management of Crohn's disease and novel data challenging standard clinical practice are some of the inflammatory bowel disease (IBD) highlights from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School, Boston, Massachusetts.

Dr Feuerstein begins by discussing two studies of upadacitinib induction and maintenance in Crohn's disease. Both studies showed that the drug achieved higher fistula closure and remission rates than did placebo, regardless of prior biologic therapy exposure.

The third study chosen by Dr Feuerstein asks whether early resection of ileocecal Crohn's disease might achieve better outcomes than would standard anti–tumor necrosis factor therapy. The study results suggested that early resection could postpone the need for medication for longer than previously thought.

More potentially practice-changing data comes from the SuPREMe-CD study, which showed that using Kono-S anastomosis reduced endoscopic recurrence of Crohn's disease compared with traditional side-to-side anastomosis.

Dr Feuerstein next discusses an analysis of the SAPPHIRE Registry, which found that IBD treatments were not linked to cancer risk. In closing, he reports on a study that showed longer withdrawal time during colonoscopy, meaning longer time spent examining the colon, is associated with improved detection of polypoid dysplasia.

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships.

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Upadacitinib in the management of Crohn's disease and novel data challenging standard clinical practice are some of the inflammatory bowel disease (IBD) highlights from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School, Boston, Massachusetts.

Dr Feuerstein begins by discussing two studies of upadacitinib induction and maintenance in Crohn's disease. Both studies showed that the drug achieved higher fistula closure and remission rates than did placebo, regardless of prior biologic therapy exposure.

The third study chosen by Dr Feuerstein asks whether early resection of ileocecal Crohn's disease might achieve better outcomes than would standard anti–tumor necrosis factor therapy. The study results suggested that early resection could postpone the need for medication for longer than previously thought.

More potentially practice-changing data comes from the SuPREMe-CD study, which showed that using Kono-S anastomosis reduced endoscopic recurrence of Crohn's disease compared with traditional side-to-side anastomosis.

Dr Feuerstein next discusses an analysis of the SAPPHIRE Registry, which found that IBD treatments were not linked to cancer risk. In closing, he reports on a study that showed longer withdrawal time during colonoscopy, meaning longer time spent examining the colon, is associated with improved detection of polypoid dysplasia.

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships.

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

A waxing and waning rash with fine scale is classic for tinea versicolor (TV). A potassium hydroxide (KOH) prep with Swartz-Lamkins stain confirmed the presence of the spaghetti-and-meatballs pattern of Malassezia furfur (MF).

TV is a skin infection caused by M furfur. TF is notorious for the variety of colors that are seen clinically, including hyperpigmentation, as seen in a recent installment in this column.¹ It can also appear as hypopigmented lesions or tan macules and patches with fine scale, as was seen in this patient. Hypopigmentation is often more pronounced on sun-exposed areas of the body. The MF produces azelaic acid. The azelaic acid blocks tyrosinase, which hinders melanocyte function and leads to hypopigmentation.² As a result, areas of skin that are affected by TV do not tan as much as the surrounding skin, making the lesions more pronounced.

First line treatment of TV includes topical antifungal preparations, such as the “azoles” (eg, clotrimazole, ketoconazole, miconazole) twice daily for 2 to 4 weeks. However, the large surface areas involved would require a large amount of these antifungal preparations that come in relatively small tubes. Thus, for many years, clinicians have turned to economical over-the-counter dandruff shampoos with either selenium sulfide or zinc pyrithione that provide excellent results. These shampoos are applied to the entire trunk at full strength, allowed to dry, and then washed off later following various timed protocols. If topical therapy is not successful, or if there is a recurrence, systemic antifungal medications are used. Oral options include fluconazole 200 mg to 300 mg orally once a week for 2 weeks and itraconazole 200 mg orally once a day for 7 days.³ Ketoconazole is avoided as a systemic antifungal (except in life-threatening situations) due to its higher rate of liver dysfunction.

This patient was instructed to apply full-strength selenium sulfide shampoo to his entire trunk in the evening, allow it to dry, then wash it off the next morning and repeat in 1 week. An alternate regimen is to leave it on for 1 hour before washing and repeat daily for 1 week. At the patient’s follow-up appointment a month later, the rash and itching had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

A waxing and waning rash with fine scale is classic for tinea versicolor (TV). A potassium hydroxide (KOH) prep with Swartz-Lamkins stain confirmed the presence of the spaghetti-and-meatballs pattern of Malassezia furfur (MF).

TV is a skin infection caused by M furfur. TF is notorious for the variety of colors that are seen clinically, including hyperpigmentation, as seen in a recent installment in this column.¹ It can also appear as hypopigmented lesions or tan macules and patches with fine scale, as was seen in this patient. Hypopigmentation is often more pronounced on sun-exposed areas of the body. The MF produces azelaic acid. The azelaic acid blocks tyrosinase, which hinders melanocyte function and leads to hypopigmentation.² As a result, areas of skin that are affected by TV do not tan as much as the surrounding skin, making the lesions more pronounced.

First line treatment of TV includes topical antifungal preparations, such as the “azoles” (eg, clotrimazole, ketoconazole, miconazole) twice daily for 2 to 4 weeks. However, the large surface areas involved would require a large amount of these antifungal preparations that come in relatively small tubes. Thus, for many years, clinicians have turned to economical over-the-counter dandruff shampoos with either selenium sulfide or zinc pyrithione that provide excellent results. These shampoos are applied to the entire trunk at full strength, allowed to dry, and then washed off later following various timed protocols. If topical therapy is not successful, or if there is a recurrence, systemic antifungal medications are used. Oral options include fluconazole 200 mg to 300 mg orally once a week for 2 weeks and itraconazole 200 mg orally once a day for 7 days.³ Ketoconazole is avoided as a systemic antifungal (except in life-threatening situations) due to its higher rate of liver dysfunction.

This patient was instructed to apply full-strength selenium sulfide shampoo to his entire trunk in the evening, allow it to dry, then wash it off the next morning and repeat in 1 week. An alternate regimen is to leave it on for 1 hour before washing and repeat daily for 1 week. At the patient’s follow-up appointment a month later, the rash and itching had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

A waxing and waning rash with fine scale is classic for tinea versicolor (TV). A potassium hydroxide (KOH) prep with Swartz-Lamkins stain confirmed the presence of the spaghetti-and-meatballs pattern of Malassezia furfur (MF).

TV is a skin infection caused by M furfur. TF is notorious for the variety of colors that are seen clinically, including hyperpigmentation, as seen in a recent installment in this column.¹ It can also appear as hypopigmented lesions or tan macules and patches with fine scale, as was seen in this patient. Hypopigmentation is often more pronounced on sun-exposed areas of the body. The MF produces azelaic acid. The azelaic acid blocks tyrosinase, which hinders melanocyte function and leads to hypopigmentation.² As a result, areas of skin that are affected by TV do not tan as much as the surrounding skin, making the lesions more pronounced.

First line treatment of TV includes topical antifungal preparations, such as the “azoles” (eg, clotrimazole, ketoconazole, miconazole) twice daily for 2 to 4 weeks. However, the large surface areas involved would require a large amount of these antifungal preparations that come in relatively small tubes. Thus, for many years, clinicians have turned to economical over-the-counter dandruff shampoos with either selenium sulfide or zinc pyrithione that provide excellent results. These shampoos are applied to the entire trunk at full strength, allowed to dry, and then washed off later following various timed protocols. If topical therapy is not successful, or if there is a recurrence, systemic antifungal medications are used. Oral options include fluconazole 200 mg to 300 mg orally once a week for 2 weeks and itraconazole 200 mg orally once a day for 7 days.³ Ketoconazole is avoided as a systemic antifungal (except in life-threatening situations) due to its higher rate of liver dysfunction.

This patient was instructed to apply full-strength selenium sulfide shampoo to his entire trunk in the evening, allow it to dry, then wash it off the next morning and repeat in 1 week. An alternate regimen is to leave it on for 1 hour before washing and repeat daily for 1 week. At the patient’s follow-up appointment a month later, the rash and itching had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Study results of microbiotic therapeutics for Clostridioides difficile infection (CDI) and a microbial dietary score that points to increased cancer risk are the microbiome advances from Digestive Disease Week 2023, as selected by Dr Purna Kashyap, from the Mayo Clinic in Rochester, Minnesota. 

Dr Kashyap starts with four studies examining microbiotic therapeutics for patients with CDI; the first two looked at RBX2660, which was recently approved by the US Food and Drug Administration (FDA). 

The first study showed that clonal engraftment of RBX2660 microbiota was associated with clinical response to the treatment, while the second indicated that the therapy is safe and effective in immunocompromised patients. 

Next, Dr Kashyap discusses a study of SER-109, also recently approved by the FDA. ESOSPOR IV revealed that the oral microbiome therapeutic achieved durable responses, even in patients with two or more CDI recurrences.  

After discussing a final CDI study that may provide a mechanism for the effectiveness of the live biotherapeutic VE303, he moves on to colon cancer. 

Dr Kashyap explains that a microbial dietary score was found to be associated not only with low-quality diets but also with an increased risk for colorectal cancer. 

--

Purna C. Kashyap, MBBS, Professor of Medicine and Physiology; Consultant, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 

Purna C. Kashyap, MBBS, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Study results of microbiotic therapeutics for Clostridioides difficile infection (CDI) and a microbial dietary score that points to increased cancer risk are the microbiome advances from Digestive Disease Week 2023, as selected by Dr Purna Kashyap, from the Mayo Clinic in Rochester, Minnesota. 

Dr Kashyap starts with four studies examining microbiotic therapeutics for patients with CDI; the first two looked at RBX2660, which was recently approved by the US Food and Drug Administration (FDA). 

The first study showed that clonal engraftment of RBX2660 microbiota was associated with clinical response to the treatment, while the second indicated that the therapy is safe and effective in immunocompromised patients. 

Next, Dr Kashyap discusses a study of SER-109, also recently approved by the FDA. ESOSPOR IV revealed that the oral microbiome therapeutic achieved durable responses, even in patients with two or more CDI recurrences.  

After discussing a final CDI study that may provide a mechanism for the effectiveness of the live biotherapeutic VE303, he moves on to colon cancer. 

Dr Kashyap explains that a microbial dietary score was found to be associated not only with low-quality diets but also with an increased risk for colorectal cancer. 

--

Purna C. Kashyap, MBBS, Professor of Medicine and Physiology; Consultant, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 

Purna C. Kashyap, MBBS, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Study results of microbiotic therapeutics for Clostridioides difficile infection (CDI) and a microbial dietary score that points to increased cancer risk are the microbiome advances from Digestive Disease Week 2023, as selected by Dr Purna Kashyap, from the Mayo Clinic in Rochester, Minnesota. 

Dr Kashyap starts with four studies examining microbiotic therapeutics for patients with CDI; the first two looked at RBX2660, which was recently approved by the US Food and Drug Administration (FDA). 

The first study showed that clonal engraftment of RBX2660 microbiota was associated with clinical response to the treatment, while the second indicated that the therapy is safe and effective in immunocompromised patients. 

Next, Dr Kashyap discusses a study of SER-109, also recently approved by the FDA. ESOSPOR IV revealed that the oral microbiome therapeutic achieved durable responses, even in patients with two or more CDI recurrences.  

After discussing a final CDI study that may provide a mechanism for the effectiveness of the live biotherapeutic VE303, he moves on to colon cancer. 

Dr Kashyap explains that a microbial dietary score was found to be associated not only with low-quality diets but also with an increased risk for colorectal cancer. 

--

Purna C. Kashyap, MBBS, Professor of Medicine and Physiology; Consultant, Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 

Purna C. Kashyap, MBBS, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5